Reaction #70671

Reaction equation

m-toluidine

2-(3-bromophenyl)-1,3-dioxolane

Sodium tert-butoxide

tri-tert-butylphosphine

→

N-(3-(1,3-dioxolan-2-yl)phenyl)-3-methylaniline

Solvents

toluene

Conditions

Workup

1. 1
   OtherTo a clean and dry 500 ml round bottom flask
2. 2
   Otherequipped with a reflux condenser and magnetic stir bar nitrogen
3. 3
   Otherwas purged
4. 4
   workup.ADDITIONanhydrous toluene (250.0 ml) was added by cannula
5. 5
   OtherThe reaction solution was purged with a strong nitrogen flow for 30 minutes
6. 6
   TemperatureThe vessel was heated
7. 7
   Temperatureto reflux for approximately 4 hours
8. 8
   Filtrationfiltered through a Celite and silica gel pad
9. 9
   OtherSolvent was removed by rotary evaporation
10. 10
    workup.DISSOLUTIONThe crude material was partially dissolved in a 10% ethyl acetate/hexane solution (20.0 ml)
11. 11
    Otherpurified by flash column chromatography
12. 12
    Otherproviding near pure product
13. 13
    OtherFurther purification

Procedure

To a clean and dry 500 ml round bottom flask equipped with a reflux condenser and magnetic stir bar nitrogen was purged and anhydrous toluene (250.0 ml) was added by cannula. m-toluidine (5.1 ml, 0.0467 mol) was added to the reaction flask by syringe. Next, 2-(3-bromophenyl)-1,3-dioxolane (7.8 ml, 0.0513 mol) was added by syringe. The reaction solution was purged with a strong nitrogen flow for 30 minutes. Sodium tert-butoxide (6.73 g, 0.0701 mol) and Pd2dba3 (0.85 g, 0.0009 mol) were then added manually, followed by the addition of tri-tert-butylphosphine (0.57 g, 0.0028 mol) in toluene (˜8 ml) via syringe. The vessel was heated to reflux for approximately 4 hours. The reaction was then cooled to room temperature and filtered through a Celite and silica gel pad. Solvent was removed by rotary evaporation. The crude material was partially dissolved in a 10% ethyl acetate/hexane solution (20.0 ml) and purified by flash column chromatography providing near pure product. Further purification was carried out using an automatic column chromatography system using 5% ethyl acetate/hexane as an eluent. This provided pure product confirmed by NMR.

Source